Add-on adefovir dipivoxil versus switch-to entecavir therapy in chronic hepatitis B patients with suboptimal response to lamivudine / 中华临床感染病杂志

ABSTRACT

Objective To compare the efficacy of add-on adefovir dipivoxil (ADV) therapy and switch-to entecavir (ETV) monotherapy in chronic hepatitis B (CHB) patients with suboptimal response to lamivudine (LAM).Methods A prospective study was performed in 120 CHB patients from Zhuji People' s Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine during June 2010 and June 2011.All patients previously received more than 24 weeks LAM treatment,but HBV DNA was still positive.Patients were randomized assigned to two groups60 patients received add-on ADV therapy and another 60 switched to ETV monotherapy.Both groups were treated for 48 weeks.Liver and kidney function,alpha-fetal protein (AFP),HBV serum markers,HBV DNA and prothrombin time (PT) were examined,and ultrasonography or CT scan of liver was performed every 1-3 months.x2 test was used to compare the HBV DNA negative rates,HBeAg seroconversion rates,resistance rates and adverse reaction at week 48 between two groups.Results Thirty-three out of 38 patients (86.8％) with baseline HBV DNA 103-105 copies/mL became HBV DNA negative after add-on ADV treatment for 48 weeks,twenty-seven out of 39 patients (69.2％) with baseline HBV DNA 103-105 copies/ml became HBV DNA negative after switch-to ETV treatment.There was a statistical difference between two groups (x2 =4.578,P ＜ 0.05).Sixteen out of 22 patients (72.7％) with baseline HBV DNA ＞ 105 copies/mL became HBV DNA negative after add-on ADV treatment for 48 weeks,while only 52.4％ (11/21) patients achieved HBV DNA negative in the switch-to ETV group.There was also a statistical difference between two groups (x2 =4.865,P ＜0.05).None of patients in add-on group developed virological breakthrough and resistance,while 5 patients in switch-to ETV group developed virogical breakthrough and 3 patients developed genetic mutation.Among them,rtM204V + rtL180M + rtS202G mutation was detected in 2 patients,and rtM204V + rtL180M +rtT184A mutation was detected in 1 patient; all mutations happened in the baseline HBV DNA ＞ 105 copies/mL group.Conclusion The add-on ADV therapy is better in viral inhibition than switch-to ETV therapy for CHB patients with suboptimal response to LAM,and it can reduce the occurrence of drug resistance.